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Cellular Mechanisms of Aging in the Werner Syndrome

  • Osamu Nikaido
  • Taka Nishida
  • Akihiro Shiga
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 190)

Abstract

The Werner syndrome (WS) is a rare autosomal recessive disease with characteristic features of accelerated ageing such as gray hair, dwarfism, juvenile cataract1), urinary excretion of high levels of acidic glycosaminoglycans2) and a short life span. Many attempts to elucidate the relatively short life spans of patients with various progeroid syndromes by using cultured cells have been made in the past two decades3,4). Among them, the reduction in population doubling numbers (PDs) in cells derived from the patients with genetic disorders such as WS3) and Hutchinson-Gilford progeria4) gave us a clue to the finding of a causal relationship between the clinical symptoms and biological defects found in these cells.

Keywords

Herpes Simplex Virus Ataxia Telangiectasia Ataxia Telangiectasia Werner Syndrome Label Intensity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    C.J. Epstein, G.M. Martin, A.S. Schultz, and A.G. Motulsky, Werner’s syndrome. A review of its symptomatology, natural history, pathologic features, genetics and relationship to the aging process, Medicine 45: 177 (1966).Google Scholar
  2. 2.
    K. Murata, Urinary acidic glycosaminoglycans in Werner’s syndrome, Experientia 38: 313 (1982).PubMedCrossRefGoogle Scholar
  3. G.M. Martin, C.A. Sprague, and C.J. Epstein, Replicative life-span of cultured human cells. Effects of donor’s age, tissue, and genotype, Lab. Invest 23:86 (1970).Google Scholar
  4. B.S. Danes, Progeria: a cell culture study on aging, J. Clin. Invest 50:2000 (1971).Google Scholar
  5. D. Salk, K. Au, H. Hoehn, and G.M. Martin, Cytogenetics of Werner’s syndrome cultured skin fibroblasts: varigated translocation mosaicism, Cytogenet. Cell Genet 30:92 (1981).Google Scholar
  6. 6.
    R. Holliday, J.S. Porterfield, and D.D. Gibbs, Premature ageing and occurrence of altered enzyme in Werner’s syndrome fibroblasts, Nature 248: 762 (1974).PubMedCrossRefGoogle Scholar
  7. 7.
    K. Tanaka, T. Nakazawa, Y. Okada, and Y. Kumahara, Roles of nuclear and cytoplasmic environments in the retarded DNA synthesis in Werner syndrome cells, Exp Cell Res. 127: 185 (1980).Google Scholar
  8. Y. Fujiwara, T. Higashikawa, and M. Tatsumi, A retarded rate of DNA replication and normal level of DNA repair in Werner’s syndrome fibroblasts in culture, J. Cell. Physiol 92:365 (1977).Google Scholar
  9. J. Epstein, J.R. Williams, and J.B. Little, Deficient DNA repair in human progeroid cells, Proc. Natl. Acad. Sci USA, 70:977 (1973).Google Scholar
  10. J. Epstein, J.R. Williams, and J.B. Little, Rate of DNA repair in progeric and normal human fibroblasts, Biochem. Biophys. Res. Comm 59:850 (1974).Google Scholar
  11. J.D. Regan and R.B. Setlow, DNA repair in human progeroid cells, Biochem. Biophys. Res. Comm 59:858 (1974).Google Scholar
  12. A.A. Francis, W.H. Lee, and J.D. Regan, The relationship of DNA excision repair of ultraviolet-induced lesions to the maximum life span of mammals, Mech. Ageing Dev. 16:181 (1981).Google Scholar
  13. R.T. Dell’Orco and W.L. Whittle, Evidence for an increased level of DNA damage in high doubling level human diploid cells in culture, Mech. Ageing Dev 15:141 (1981).Google Scholar
  14. O. Nikaido, S. Ban, and T. Sugahara, Population doubling number in cells with genetic disorders, Adv. Exp. Med. Biol 129:303 (1980).Google Scholar
  15. 15.
    V.J. Cristofalo and B.B. Sharf, Cellular senescence and DNA synthesis; Thymidine incorporation as a measure of population age in human diploid cells, Exp Cell Res. 76: 419 (1973).PubMedCrossRefGoogle Scholar
  16. 16.
    A. Maieira-Coelho, Kinetics of the proliferation of human fibroblasts during their life span in vitro, Mech. Ageing Dev. 6: 341 (1977).CrossRefGoogle Scholar
  17. 17.
    E.L. Schneider and B.J. Fowlkes, Measurement of DNA content and cell volume in senescent human fibroblasts utilizing flow multiparameter single cells analysis, Exp. Cell Res. 98: 298 (1976).PubMedCrossRefGoogle Scholar
  18. 18.
    F. Hanaoka and M. Yamada, Autoradiographic studies of DNA replication in Werner’s syndrome, in: “Pathogenetic Mechanisms in Werner’s Syndrome and Their Role in Human Aging,” US-Japan cooperative seminar, Kobe, Japan (1982).Google Scholar
  19. S. Ban, 0. Nikaido, and T. Sugahara, Acute and late effects of a single exposure of ionizing radiation on cultured human diploid cell population, Radiat. Res 81:120 (1980).Google Scholar
  20. 20.
    S. Fujita, T. Ashihara, and M. Fukuda, Simultaneous measurement of DNA content and grain count on an autoradiograph of Feulgen stained cells, Histochem 40: 155 (1974).Google Scholar
  21. A. Shima and T. Sugahara, Age-dependent ploidy class changes in mouse hepatocyte nuclei as revealed by Feulgen-DNA cytofluorometry, Exp. Gerontol 11:193 (1976).Google Scholar
  22. C.A. Neill and M.M. Dingwall, A syndrome resembling progeria: a review of 2 cases, Arch. Dis. Child 25:213 (1950).Google Scholar
  23. 23.
    M. Ikenaga, M. Inoue, T. Kozuka, and T. Sugita, The recovery of colony-forming ability and the rate of semi-conservative DNA synthesis in ultraviolet-irradiated Cockayne and normal cells, Mutation Res 91: 87 (1981).Google Scholar
  24. M.C. Paterson, B.P. Smith, P.H.M. Lohman, A.K. Anderson, and L. Fishman, Defective excision repair of gamma-ray-damaged DNA in human (ataxia telangiectasia) fibroblasts, Nature 260:444 (1976).Google Scholar
  25. 25.
    R.A. Vincent, and P.C. Huang, The proportion of cells labeled with tritiated thymidine as a function of population doubling level in cultures of fetal, adult, mutant, and tumor origin, Exp Cell Res. 102: 31 (1976).Google Scholar
  26. R. Yanishevski, M.L. Mendelsohn, B.H. Mayall, and V.J. Cristofalo, Proliferative capacity and DNA content of aging human diploid cells in culture: cytophotometric and autoradiographic analysis, J. Cell. Physiol 84:165 (1974).Google Scholar
  27. E.L. Schneider and Y. Mitsui, The relationship between in vitro aging and in vivo human age, Proc. Nati. Acad. Sci USA. 73:3584 (1976).Google Scholar
  28. R.W. Hart and R.B. Setlow, Correlation between deoxyribonucleic acid excision-repair and life span in a number of mammalian species, Proc. Natl. Acad. Sci. USA 71:2169 (1974).Google Scholar
  29. 29.
    L. Hayflick, The longevity of cultured human cells, J. Am. Geriatr Soc. 22: 1 (1974).PubMedGoogle Scholar
  30. 30.
    K. Hall, C. Albrightson, and R.W. Hart, A direct relationship among primates between maximum lifespan and DNA repair. Abstract of 11th Int. Congr. Gerontology, Tokyo, 1978.Google Scholar
  31. V. Paffenholtz, Correlation between DNA repair of embryonic fibroblasts and different life span of 3 inbred mouse strains, Mech. Ageing Dev. 7:131 (1978).Google Scholar
  32. 32.
    H. Kato, M. Harada, K. Tsuchiya, and K. Moriwaki, Absence of correlation between DNA repair in ultraviolet irradiated mammalian cells and life span of the donor species, Japan J. Genetics 55: 99 (1980).Google Scholar
  33. 33.
    C.D. Lytle, 0. Nikaido, V.M. Hitchins, and E.D. Jacobson, Host cell reactivation by excision repair is error-free in human cells, Mutation Res 94: 405 (1982)Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Osamu Nikaido
    • 1
  • Taka Nishida
    • 1
  • Akihiro Shiga
    • 2
  1. 1.Division of Radiation Biology Faculty of Pharmaceutical SciencesKanazawa UniversityKanazawa 920Japan
  2. 2.Department of Experimental RadiologyShiga University of Medical ScienceOhtsuJapan

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